Ecosystem & Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4Z6.
Environ Toxicol. 2012 Mar;27(4):244-54. doi: 10.1002/tox.20635. Epub 2010 Aug 19.
Subchronic exposure to arsenic in rats was investigated to identify sensitive indicators of subclinical toxicity in rats. Immunological, pathological, and biochemical bioindicators were examined in rats exposed to arsenic in their drinking water. Juvenile male Wistar rats were allocated to four treatment groups receiving 0, 0.4, 4, and 40 ppm of arsenite in drinking water for 18 wks. Besides daily monitoring for clinical signs of adverse health effects, clinical biochemistry, B-cell-mediated and innate immune responses, plus gross, and histopathology were examined. In vitro tests of oxidative damage to basic cellular constituents, lipids, proteins, and nucleic acids, were measured using thiobarbituric acid reacting substances (TBARS) assays, protein carbonyl formation, and 8-hydroxydeoxyguanosine (8-OHdG), respectively. Clinical changes in the rats were limited to decreased feed and water intake in the high- (40 ppm) dose group (P < 0.05), however, growth rate was not affected. Serum biochemical changes occurred in blood urea nitrogen, K(+) , Cl(-) , and alanine aminotransferase (ALT) from arsenic exposure. Immunotoxicity was evident through a dose-dependent suppression of the secondary antibody-mediated response to a T-cell-dependent antigen, keyhole limpet hemocyanin (KLH). Histopathology of the liver revealed marked fatty infiltration and vacuolization particularly evident in periacinar hepatocytes. This pattern of toxicopathology in the high-exposure group may be related to the significantly higher (P < 0.05) oxidative stress, demonstrated through lipid peroxidation (TBARS assay) in the rats exposed to 40 ppm arsenite. The present study revealed that young, growing rats exposed to arsenic for 18 wks tolerated exposures up to 4 ppm. At higher doses, there was evidence of hepatotoxicity, humoral immunity was compromised, and an adverse effect on hepatic organelle and cell membranes was evident through a dose dependent increased in oxidative stress.
本研究旨在探讨大鼠亚慢性砷暴露，以确定亚临床毒性的敏感指标。在饮水中摄入砷的大鼠中，检测了免疫、病理和生化生物标志物。将幼年雄性 Wistar 大鼠分为四组，分别接受 0、0.4、4 和 40ppm 亚砷酸盐的饮用水，为期 18 周。除了每天监测不良健康影响的临床症状外，还检查了临床生物化学、B 细胞介导和先天免疫反应以及大体和组织病理学。使用硫代巴比妥酸反应物质（TBARS）测定法、蛋白质羰基形成和 8-羟基脱氧鸟苷（8-OHdG）分别测量了基本细胞成分、脂质、蛋白质和核酸的氧化损伤的体外试验。在高剂量（40ppm）组中，大鼠的临床变化仅限于饲料和水摄入量减少（P <0.05），但生长速度不受影响。血清生化变化发生在血尿素氮、K（+）、Cl（-）和丙氨酸氨基转移酶（ALT）从砷暴露中。免疫毒性通过依赖于 T 细胞的抗原（匙孔血蓝蛋白（KLH））的二次抗体介导反应的剂量依赖性抑制而明显。肝脏的组织病理学显示，肝实质细胞的脂肪浸润和空泡化明显，尤其是在近肝实质细胞中。这种高暴露组的毒性病理学模式可能与脂质过氧化（TBARS 测定法）在暴露于 40ppm 亚砷酸盐的大鼠中表现出的更高（P <0.05）氧化应激有关。本研究表明，18 周内接触砷的年轻、生长中的大鼠耐受 4ppm 以下的暴露。在较高剂量下，有肝毒性的证据，体液免疫受损，并且通过剂量依赖性增加氧化应激，对肝细胞器和细胞膜有不利影响。
